ABSTRACT
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease that affects both the articular and extra-articular structures, leading to significant joint damage, disability and excess mortality. The treatment algorithm of RA has changed tremendously in the past 1–2 decades because of the emergence of novel biological therapies that target different mechanisms of action in addition to TNFα.
Areas covered
This article summarizes the evidence and safety of the non-TNF biological DMARDs in the treatment of RA, including those that target B cells, T-cell co-stimulation, interleukin (IL)-6 and granulocyte-monocyte colony-stimulating factor (GM-CSF). The targeted synthetic DMARDs such as the Janus kinase inhibitors are not included. The availability of the less costly biosimilars has enabled more patients to receive biological therapy earlier in the course of the disease. The evidence for the non-TNF biosimilar compounds in RA is also reviewed.
Expert opinion
There are unmet needs of developing novel therapeutic agents to enhance the response rate and provide more options for difficult-to-treat RA. These include the newer generation biologic and targeted synthetic DMARDs. A personalized treatment strategy in RA requires evaluation of the cellular, cytokine, genomic and transcriptomic profile that would predict treatment response to biologic or targeted DMARDs of different mechanisms of action.
Article highlights
A number of non-TNF biological agents that target the B cells, T-cell co-stimulation, IL-6 and GM-CSF have been developed for the treatment of RA. These compounds provide important options for difficult-to-treat RA.
Early treatment with the treat-to-target (T2T) principle is an important strategy for RA independent of the use of the novel b/tsDMARDs.
A personalized treatment strategy in RA requires evaluation of the cellular, cytokine, genomic and transcriptomic profile that would predict treatment response to biologic or targeted DMARDs of different mechanisms of action.
The availability of the less costly biosimilar compounds (bsDMARDs) may enable more RA patients to receive biological treatment earlier in the course of disease. This will ultimately help to improve the prognosis of the disease.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
A reviewer on this manuscript has disclosed research support (paid to their institution) from Biogen and Galapagos NV; consultancy for Alvotech Swiss AG, Boehringer Ingelheim GmbH, Biohaven Pharmaceuticals, Inc., Bristol Myers Squibb Co., Fresenius Kabi, Novartis Pharmaceuticals Corp., Pfizer Inc., Samsung Bioepis, Teijin Pharma Ltd., Viatris Inc., UCB Inc. and Yuhan Corp.; independent data monitoring committee member for Inmagene LLC (relationship ended) and Kolon TissueGene, Inc.; and royalties from Wolters Kluwer NV (for UpToDate). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.